Differential effects of glycosphingolipids on protein kinase C activity in PC12D pheochromocytoma cells

Robert K Yu, Toshio Ariga, Hiide Yoshino, Ritsuko Katoh-Semba, Shunlin Ren

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Previous studies have shown that certain glycosphingolipids may function as modulators of protein kinase C (PKC) activity. To study the structure-activity relationship, we examined the effects of 17 gangliosides, 10 neutral glycolipids, as well as sulfatide, psychosine and ceramide on PKC activity in PC12D cells. Using an in vitro assay system, we found that all but one (GQ1b) ganglioside inhibited PKC activity at concentrations between 25 and 100 μM, and the potency was proportional to the number of sialic acid residues. However, at lower concentrations several gangliosides, including GM1 and LM1 behaved as mild activators of PKC activity. GQ1b had no effect within the range 0.1-10 μM, but acted as a mild activator of PKC activity at 25 μM. On the other hand, fucosyl-GM1 and GM1 containing blood group B determinant, which are abundant in PC12 cells, were potent inhibitors of PKC activity. Among the neutral glycosphingolipids tested, LacCer, Gb3, GalGb3, and GA1, all of which have a terminal galactose residue, were found to be ineffective or acted as mild activators of PKC activity. In contrast, GA2, Gb4 and Gb5 which have a terminal N-acetylgalactosamine residue, were potent inhibitors of the PKC activity. Thus, the terminal sugar residue may play a pivotal role in determining the effect of glycosphingolipids in modulating PKC activity. In addition, we also found that GalCer containing normal fatty acids acted as potent activators of PKC activity. Ceramide and GlcCer appeared to be ineffective in modulating PKC activity, whereas psychosine and sulfatides appeared to be inhibitory. We conclude that the carbohydrate head groups and the hydrophobic groups of gangliosides and neutral glycolipids may modulate the PKC system in unique manners, which may in turn affect various biological processes in the cell.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalJournal of Biomedical Science
Volume1
Issue number4
DOIs
StatePublished - Oct 1 1994
Externally publishedYes

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Glycosphingolipids
Pheochromocytoma
Protein Kinase C
Gangliosides
Psychosine
Sulfoglycosphingolipids
Ceramides
Glycolipids
Neutral Glycosphingolipids
G(M1) Ganglioside
Biological Phenomena
Acetylgalactosamine
PC12 Cells
N-Acetylneuraminic Acid
Structure-Activity Relationship
Blood Group Antigens
Galactose
Sugars
Modulators
Assays

Keywords

  • Gangliosides
  • Neutral glycosphingolipids
  • PC12D
  • Phenochromocytoma cells
  • Protein kinase C

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Differential effects of glycosphingolipids on protein kinase C activity in PC12D pheochromocytoma cells. / Yu, Robert K; Ariga, Toshio; Yoshino, Hiide; Katoh-Semba, Ritsuko; Ren, Shunlin.

In: Journal of Biomedical Science, Vol. 1, No. 4, 01.10.1994, p. 229-236.

Research output: Contribution to journalArticle

Yu, Robert K ; Ariga, Toshio ; Yoshino, Hiide ; Katoh-Semba, Ritsuko ; Ren, Shunlin. / Differential effects of glycosphingolipids on protein kinase C activity in PC12D pheochromocytoma cells. In: Journal of Biomedical Science. 1994 ; Vol. 1, No. 4. pp. 229-236.
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AB - Previous studies have shown that certain glycosphingolipids may function as modulators of protein kinase C (PKC) activity. To study the structure-activity relationship, we examined the effects of 17 gangliosides, 10 neutral glycolipids, as well as sulfatide, psychosine and ceramide on PKC activity in PC12D cells. Using an in vitro assay system, we found that all but one (GQ1b) ganglioside inhibited PKC activity at concentrations between 25 and 100 μM, and the potency was proportional to the number of sialic acid residues. However, at lower concentrations several gangliosides, including GM1 and LM1 behaved as mild activators of PKC activity. GQ1b had no effect within the range 0.1-10 μM, but acted as a mild activator of PKC activity at 25 μM. On the other hand, fucosyl-GM1 and GM1 containing blood group B determinant, which are abundant in PC12 cells, were potent inhibitors of PKC activity. Among the neutral glycosphingolipids tested, LacCer, Gb3, GalGb3, and GA1, all of which have a terminal galactose residue, were found to be ineffective or acted as mild activators of PKC activity. In contrast, GA2, Gb4 and Gb5 which have a terminal N-acetylgalactosamine residue, were potent inhibitors of the PKC activity. Thus, the terminal sugar residue may play a pivotal role in determining the effect of glycosphingolipids in modulating PKC activity. In addition, we also found that GalCer containing normal fatty acids acted as potent activators of PKC activity. Ceramide and GlcCer appeared to be ineffective in modulating PKC activity, whereas psychosine and sulfatides appeared to be inhibitory. We conclude that the carbohydrate head groups and the hydrophobic groups of gangliosides and neutral glycolipids may modulate the PKC system in unique manners, which may in turn affect various biological processes in the cell.

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